Transcript Se-enriched vegetables and cancer reduction: P. Whanger, Oregon

Se-enriched vegetables and cancer reduction
P. D. WHANGER, PhD.
Department of Environmental &
Molecular Toxicology
Oregon State University
Corvallis, OR. 97330
SELENIUM LEVELS
Low
Variable
Adequate
Accumulators
Epidemiological Studies
Shamberger and Frost
Can. Med. Assoc. J. 104:82 (1969)—reported inverse relationship
of selenium intake with cancer
Shamberger and Willis
CRC Crit. Rev. Clin. Lab. Sci. 2: 211 (1971)—more detailed
study showing this same inverse relationship
Schrauzer et al
Bioinorganic Chem. 7:23 (1977)--27-country comparison
revealed certain cancers varied inversely with estimated per
capita selenium intake
Selenium and Tumors with Small Animals
There have been over 100 experiments conducted
(Combs and Gray, Pharmacol. Ther. 79: 179 (1998)
(a) Two-thirds of animal studies showed
statistically significant reductions of tumors by selenium
(b)One-half showed reductions of 50% or more by selenium
Effects of Selenium on Cancer in Humans
Modified From J. Amer. Med. Assoc. 276: 1957 (1996)
GSSeH
GSSG
H2Se
GSSeSG
Acetylserine
GSH
Acetate
SeO3
-glutamyl Selenocystathionine
Selenocysteine
ADP
Succinyl
homocysteine
ATP
SeO4
glutamine
Proteins
Succinate
Se-methylselenocysteine
Selenocystathionine
Se-methylSeCysSe-oxide
Selenohomocysteine
-glutamyl –Se methyl
Selenocysteine
Dimethyldiselenide
Se-methylselenomethionine
adenosine
Selenomethionine
ATP
Se-adenosyl
selenocysteine
ADP
-keto--methyl
selenobutyrate
dimethylselenopropionate
Se-adenosylselenomethionine
dimethyl selenide
General body
proteins
Selenoproteins
(as selenocysteine)
selenomethionine
SeO4
SeO3
GS-Se-SG
selenocystathionine
selenophosphate
selenocysteine
GS-SeH
H2Se
-keto--methyl selenobutyrate
CH3SeH
methyl seleno propionate
(CH3)2Se
Se-methyl selenocysteine
(CH3)3Se+
-glutamyl-Se-methyl selenocysteine
Anticarcinogenic Efficacy of Different Selenium Compounds
for Reduction of Mammary Tumors in Rats
Mammary Tumors in Rats Fed Various Diets
Nutr. Cancer 17:279 (1992)
Effect of Selenium on the Incidence of Tumors in Rats
Injected with Methylnitrosourea
Mammary Cancer Prevention in Rats Fed Different
Sources of Selenium
Effect of Dietary Form of Selenium on Tissue Selenium
Concentrations in Rats
J. Agric Food Chem. 49: 2681 (2001)
Tissue Selenium Levels in Rats Fed Different
Sources of Selenium
Carcinogenesis 15: 573 (1994)
Mammary cancer prevention by selenium enriched garlic or
selenium enriched yeast in the DMBA and MNU models
Percent Composition of Identified Selenium Species
of Selenized Garlic and Yeast
J. Agric Chemistry, 48:2065 (2000)
Figure 6. Structures of -glutamyl-Se-methylselenocysteine,
Se-methylselenocysteine, and selenomethionine.
NH-CO-CH2-CH2-CH(NH2)-COOH
|
CH3-Se-CH2-CH-COOH
(-glutamyl-Se-methylselenocysteine)
CH3-Se-CH2-CH2-CH(NH2)-COOH
(Selenomethionine)
CH3-Se-CH2-CH(NH2)-COOH
(Se-methylselenocysteine)
J. Agric. Food Chem., Vol: 48, No. 6, 2000
Percentages of Total Selenium as SeMCYS
in Selenium Enriched Plants
Plants
% Se as
SeMCYS
Ramps
35-60
Garlic
47-87
Onions
42-55
Broccoli florets
63
Broccoli sprouts
45
Summarized in J. American College of Nutrition 21: 223 (2002)
Effect of Dietary Form of Selenium on Total Number
of Aberrant Crypt Foci in Rats
J. Agric Food Chem. 49: 2681 (2001)
Effect of Dietary Form and Amount of Selenium on Colon Tumors in Rats
J. Nutr. 130:2384 (2000)
Wheat and Broccoli
• High Selenium wheat reduced colon tumors in
rats but selenomethionine was not very
effective in this reduction. Biofactors 14: 191 (2001).
• High selenium broccoli reduced colon tumors
in rats, but will SEMCYS be effective (Finley,
personal communication)
• SELENOMETHIONINE
- Primary form of Se in enriched
yeast, wheat, corn, rice and
soybeans
• Se-METHYLSELENOCYSTEINE
- Primary form of Se in Astragalus,
enriched garlic, broccoli (florets and
sprouts), onions and ramps
Uptake of Selenium from Soil versus Leaves
Se in broccoli µg/gm
400
300
200
100
0
Addition to soil
Sprayed on Leaves
Effects of Sticker on the Uptake of Selenium by Broccoli
Se conc. in Sprouts (µg/g)
Selenium Uptake by Broccoli Sprouts
300
200
100
0
0
10
20
Se concentration in water (µg/ml)
30
Conclusions
1. Selenium enriched garlic, broccoli florets, onions and
ramps significantly reduced mammary tumors in rats.
2. Selenium enriched broccoli (florets and sprouts) and wheat
reduced colon tumors in rats.
3. These selenium enriched vegetables did not result in
excessive tissue accumulation of selenium and thus are
safe for human consumption.
4. SeMCYS is the most effective selenocompound in plants
for reduction of mammary tumors in rats. Methylselenol
appears to be the specific selenocompound that is
effective against mammary tumors.
Accumulation of Selenium in
blood, kidney, and liver from
rats fed a selenium-enriched diet
Control =
SEL =
SeM =
SeR =
basal diet
selenate
selenomethionine
Se-enriched ramps
Accumulation of Selenium in
muscle and testes from rats
fed a selenium-enriched diet
Control
SEL
SeM
SeR
SeR+SeM
Schematic flow chart showing the main sites where selenobetaine,
Se-methyselenocysteine, selenobetaine methyl ester, and dimethylselenoxide enter the selenium metabolic pathway.
Selenium in Biology and Human Health, p 173, Springer Verlag, New York
Wheat and Broccoli
• High selenium wheat reduced colon
tumors
Acknowledgment
My collegues: C. Ip (Roswell Park
Cancer Institute, Buffalo, NY; C.
Polan and G. Welbaum, Virginia
Technical University; and P. Uden,
University of Massachusetts.
Acknowledgment
• We are grateful to Judy Butler and Yu Sun for
doing the selenium analyses and the
bioavailability study
• Thanks to R. Hafez and M. Kotrebai for the
selenium speciation.
• Thanks to Wendy Werks, John Chandler;
Johnny, Ruby, Harvey and Debbie Whanger;
Jeannie, Keith, Zemry and Margaret Lou
Crookshanks; Wayne and Beverly Hinkle; and
Bill Definbaugh who worked on various aspects
of this project.